Adenosine deaminase augments SARS-CoV-2 specific cellular and humoral responses in aged mouse models of immunization and challenge

Abstract Despite numerous clinically available vaccines and therapeutics, aged patients remain at increased risk for COVID-19 morbidity mortality. Furthermore, the patient population has suboptimal responses to SARS-CoV-2 vaccine antigens. Here, we characterized vaccine-induced synthetic DNA antigens in mouse models. Aged mice had altered cellular responses, including decreased IFNγ secretion TNFα as compared young mice. significantly binding neutralizing antibodies their serum counterparts. Co-immunization with plasmid-encoded molecular adjuvant adenosine deaminase-1 (pADA) enhanced expanded breadth affinity of humoral pADA co-delivery also gene expression profiles lymph node lymphocytes animals. scRNAseq analysis nodes revealed that co-immunization supported a strong T H1 profile FoxP3 expression. Upon challenge viral loads age-associated mortality mouse-adapted ACE2 transgenic These data support use model decreases immunogenicity infection-mediated context SARS-CoV-2. studies provide further deaminase elderly. This work was by NIH NCI award T32 CA09171 (ENG) NIAID T32-AI-055400 (EMP) The Wistar Institute coronavirus discovery fund additional from CEPI/Inovio Pharmaceuticals.